NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Nov 14, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001090508.52

Allele description [Variation Report for NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu)]

NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu)

Gene:

SERPINC1:serpin family C member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q25.1

Genomic location:

Preferred name:

NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu)

Other names:

P41L; NM_000488.3(SERPINC1):c.218C>T

HGVS:

NC_000001.11:g.173914743G>A
NG_012462.1:g.7636C>T
NM_000488.4:c.218C>TMANE SELECT
NM_001365052.2:c.74C>T
NM_001386302.1:c.218C>T
NM_001386303.1:c.299C>T
NM_001386304.1:c.218C>T
NM_001386305.1:c.218C>T
NM_001386306.1:c.218C>T
NP_000479.1:p.Pro73Leu
NP_000479.1:p.Pro73Leu
NP_001351981.1:p.Pro25Leu
NP_001373231.1:p.Pro73Leu
NP_001373232.1:p.Pro100Leu
NP_001373233.1:p.Pro73Leu
NP_001373234.1:p.Pro73Leu
NP_001373235.1:p.Pro73Leu
LRG_577t1:c.218C>T
LRG_577:g.7636C>T
LRG_577p1:p.Pro73Leu
NC_000001.10:g.173883881G>A
NM_000488.3:c.218C>T
P01008:p.Pro73Leu

Protein change:

P100L; PRO41LEU

Links:

UniProtKB: P01008#VAR_007036; OMIM: 107300.0012; dbSNP: rs121909551

Molecular consequence:

NM_000488.4:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001365052.2:c.74C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386302.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386303.1:c.299C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386304.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386305.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386306.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001246102	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Sep 1, 2021)	germline	clinical testing	Citation Link,
SCV001820746	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 14, 2025)	germline	clinical testing	Citation Link,
SCV002573725	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 21, 2025)	germline	clinical testing	PubMed (20) [See all records that cite these PMIDs] 2012760, 2372510, 23910795, 24082793, 24196373, 24956267, 25466846, 25837307, 2615648, 26748602, 2794060, 28300866, 29153735, 30721820, 33917853, 34800304, 37201530, 7455996, 7734360, 25741868
SCV005198210	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV007598995	Dasa	criteria provided, single submitter (DASA Assertion Criteria)	Pathogenic (Jul 31, 2025)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 2794060, 3080419, 23910795, 24082793, 24956267, 26748602, 28300866, 28317092 Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	10	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The incidence of dysfunctional antithrombin variants: four cases in 210 patients with thromboembolic disease.

Harper PL, Luddington RJ, Daly M, Bruce D, Williamson D, Edgar PF, Perry DJ, Carrell RW.

Br J Haematol. 1991 Mar;77(3):360-4.

PubMed [citation]

PMID:: 2012760

Clinical and biochemical characterization of antithrombin III Franconville, a variant with Pro 41 Leu mutation.

de Roux N, Chadeuf G, Molho-Sabatier P, Plouin PF, Aiach M.

Br J Haematol. 1990 Jun;75(2):222-7.

PubMed [citation]

PMID:: 2372510

See all PubMed Citations (22)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001246102.38

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From GeneDx, SCV001820746.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate defects in heparin binding properties (PMID: 22498748, 27322195); Reported previously as P41L or AT Basel using alternate nomenclature; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24196373, 24956267, 26748602, 31064749, 22498748, 25637381, 3080419, 28317092, 2794060, 23910795, 27322195, 24082793, 29902631, 28300866, 30721820, 25837307, 34426522, 31589614, 33614741, 36764659, 34653293, 33917853, 34800304, 37201530)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV002573725.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	not provided	clinical testing	PubMed (20)

Description

PP1_strong, PP3, PP4, PP5, PM1, PS4_very_strong

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		10	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005198210.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Dasa, SCV007598995.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu) is a missense variant that results in the substitution of proline with leucine. The affected residue or protein region has prior evidence supporting clinical relevance. Segregation evidence has been reported in affected families. Functional evidence supports a deleterious effect on the gene or gene product (PMID: 2794060; PMID: 3080419; PMID: 23910795; PMID: 24082793; PMID: 24956267). This variant has been recurrently observed in individuals with related phenotype (PMID: 2794060; PMID: 3080419; PMID: 23910795; PMID: 24082793; PMID: 24956267). Multiple computational predictions support a deleterious effect on the gene or gene product. The variant is present at low frequency in population datasets. Based on the available data, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 20, 2026

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